The flowering tops of Hypericum perforatum (St John's wort) contain a large number of structurally different substances which act directly or indirectly on the central nervous system. Among said substances, hyperforin, a phloroglucinol derivative, is one of the main constituents, together with adhyperforin, of the lipophilic fraction obtained from the flowering tops of the plant (Erdelmeier C. A. J., Pharmacopsychiatry 31, 2, 1998).
Hyperforin has formed the subject of numerous studies, which have demonstrated a potent antidepressant activity (Laakman G. et al., Pharmacopsychiatry 31, 54, 1998; Butterweck V. et al., Life Science 73, 627, 2003).
Moreover, salts with inorganic or ammonium cations of hyperforin and adhyperforin have been described as having an important action for the prophylaxis and treatment of Alzheimer's disease (WO99/41220).
It is also known from the literature that hyperforin is highly unstable under the usual extraction and storage conditions, and derivatives have been devised to improve its stability (WO99/41220, WO99/64388).
In particular, more stable hyperforin and adhyperforin derivatives have been developed by total reduction of the double bonds of the isoprene chains and reduction to hydroxyl groups of the keto groups in the 1 and 10 positions (Bystrov N. S. et al., Bioorg. Khim. 4, 791, 1978). These derivatives have proved not only more stable, but also much more effective as antidepressants, anxiolytics and anti-neurodegenerative drugs (WO03/091194).
It has now surprisingly been found that the hyperforin and adhyperforin derivatives obtainable by reduction to hydroxy groups of the ketones in the 1 and 10 position described in WO03/091194 can in turn, by hydroxylation followed by deisopropylation, give rise to novel products which cross the blood-brain barrier more efficiently and inhibit neuropathological damage induced by Aβ fibrils in different experimental models.